STEPTRACKERMICROBIOLOGY + INFECTIOUS DISEASE | HIV COMPLICATIONS | HIGH-YIELD REVIEW

HIV II — Opportunistic Infections

The CD4 count tells you which infections and cancers to expect and when to start prophylaxis — learn the ladder from 500 down to 50.

FOCUS ON

By CD4: < 500 → oral thrush, zoster, oral hairy leukoplakia, TB (any count), Kaposi; < 200 → Pneumocystis pneumonia, HIV dementia, PML, Histoplasma (< 150) → start TMP-SMX; < 100 → Toxoplasma encephalitis (ring-enhancing lesions), cryptococcal meningitis, Candida esophagitis, cryptosporidiosis, primary CNS lymphoma (EBV); < 50 → CMV retinitis/colitis, disseminated MAC, invasive Aspergillus. IRIS: paradoxical worsening after ART starts.

CD4 · INFECTION

ORGANISM

CLINICAL PICTURE

DIAGNOSIS · TREATMENT

Any count — tuberculosis

M tuberculosis

Pulmonary or extrapulmonary; atypical lower-lobe, no cavity when CD4 low

Screen with IGRA · RIPE (watch drug interactions)

< 500 — oral candidiasis

Candida albicans

White plaques that scrape off

Fluconazole or clotrimazole

< 500 — oral hairy leukoplakia

EBV

White, corrugated plaques on lateral tongue; don't scrape off

Benign marker of immunosuppression

< 200 — Pneumocystis pneumonia

Pneumocystis jirovecii (fungus)

Gradual dyspnea, dry cough, hypoxemia (worse with exertion), ↑ LDH; bilateral interstitial "ground-glass" infiltrates; pneumothorax

Silver stain of BAL · TMP-SMX + steroids if PaO₂ < 70 · prophylaxis at CD4 < 200

< 200 — PML

JC virus

Subacute focal deficits; non-enhancing white-matter lesions

ART

< 200 — HIV-associated neurocognitive disorder

HIV-infected microglia (multinucleated giant cells)

Memory loss, psychomotor slowing

ART

< 150 — histoplasmosis

Histoplasma capsulatum (Ohio/Mississippi)

Disseminated: fever, weight loss, hepatosplenomegaly, pancytopenia, oral ulcers

Urine antigen · amphotericin → itraconazole

< 100 — Toxoplasma encephalitis

Toxoplasma gondii reactivation (IgG ⁺)

Headache, confusion, focal deficits, seizures; multiple ring-enhancing lesions

Pyrimethamine + sulfadiazine + leucovorin · TMP-SMX prophylaxis

< 100 — cryptococcal meningitis

Cryptococcus neoformans (pigeon droppings)

Subacute headache, fever, ↑ opening pressure

CSF cryptococcal antigen, India ink · amphotericin + flucytosine → fluconazole; serial LPs

< 100 — Candida esophagitis

Candida

Odynophagia; white plaques on endoscopy

Empiric fluconazole

< 100 — cryptosporidiosis

Cryptosporidium parvum

Chronic severe watery diarrhea

Acid-fast oocysts in stool · ART (nitazoxanide)

< 100 — primary CNS lymphoma

EBV-driven B-cell lymphoma

Single (often periventricular) enhancing lesion

EBV DNA in CSF

< 50 — CMV

CMV reactivation

Retinitis (painless vision loss), colitis, esophagitis (large linear ulcers)

Ganciclovir, valganciclovir

< 50 — disseminated MAC

M avium complex

Fever, night sweats, weight loss, diarrhea, hepatosplenomegaly, ↑ ALP, anemia

Blood culture · clarithromycin + ethambutol · prophylaxis only if not starting ART

IRIS

Recovering immunity attacks existing pathogens

Worsening TB, MAC, cryptococcal or CMV disease weeks after ART

Continue ART; delay ART for cryptococcal meningitis

Picture it — the CD4 ladder

Infections by CD4 countEach column adds to everything above it — a patient at CD4 40 is at risk for the whole ladder. Triangles mark where prophylaxis starts.

Schematic diagrams, not to scale.

Mechanism — why low CD4 unleashes these organisms

CD4⁺ T cells lost

→

↓ IFN-γ → macrophages not activated

→

Intracellular pathogens escapeTB, MAC, Histoplasma, Toxo

↓ T-cell help

→

Latent viruses reactivateCMV, EBV, JC, HHV-8

CNS lesions in AIDS

CAUSE

IMAGING

KEY TEST

Toxoplasma

Multiple ring-enhancing

Toxo IgG, response to therapy

CNS lymphoma

Single enhancing, periventricular

EBV DNA in CSF

PML

Non-enhancing white matter

JC virus PCR

Cryptococcus

Often normal; ↑ pressure

CSF antigen

How it's tested

COMMON CONFUSIONCandida thrush scrapes off; oral hairy leukoplakia (EBV) does not.

THE TRAPRing-enhancing lesions in a Toxo-seropositive AIDS patient → treat empirically for Toxo and reimage in 2 weeks; biopsy only if no response.

YOUR APPROACHKnow the CD4 count → list the infections at or above that threshold → match organ and imaging → treat and start the right prophylaxis.

If you see… think…

CD4 150, dyspnea on exertion, bilateral ground-glass, ↑ LDH → Pneumocystis

Prophylaxis to start at CD4 < 200 → TMP-SMX

Multiple ring-enhancing brain lesions, CD4 60 → Toxoplasma

Single periventricular enhancing mass, EBV in CSF → primary CNS lymphoma

Headache, very high opening pressure, encapsulated yeast → Cryptococcus

Painful swallowing with white plaques → Candida esophagitis

Chronic watery diarrhea with acid-fast oocysts → Cryptosporidium

CD4 30 with painless vision loss → CMV retinitis

CD4 30 with fever, weight loss, ↑ ALP, positive blood culture for AFB → disseminated MAC

Lymph nodes enlarge weeks after starting ART → IRIS